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Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence


Materials engineering

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Analytical Chemistry



In this study, we have prepared thermally initiated polymeric monolithic stationary phases within discrete regions of 3D-printed titanium devices. The devices were created with controllable hot and cold regions. The monolithic stationary phases were first locally created in capillaries inserted into the channels of the titanium devices. The homogeneity of the monolith structure and the interface length were studied by scanning a capacitively coupled conductivity contactless detector (C4D) along the length of the capillary. Homogeneous monolithic structures could be obtained within a titanium device equipped with a hot and cold jacket connected to two water baths. The confinement method was optimized in capillaries. The sharpest interfaces (between monolith and empty channel) were obtained with the hot region maintained at 70 °C and the cold region at 4 or 10 °C, with the latter temperature yielding better repeatability. The optimized conditions were used to create monoliths bound directly to the walls of the titanium channels. The fabricated monoliths were successfully used to separate a mixture of four intact proteins using reversed-phase liquid chromatography. Further chromatographic characterization showed a permeability (Kf) of ∼4 × 10–15 m2 and a total porosity of 60%.

Since their introduction in the chromatographic world, porous polymer monoliths have proven to be powerful separation media. These chromatographic supports have been widely applied for applications, such as microscale liquid chromatography (LC) of peptides and proteins, but have also been used in capillary electrochromatography (CEC),(1) gas chromatography (GC),(2) sample preparation,(3) and catalysis.(4) The ease of preparation of monoliths, diverse chemistry options, and high permeabilities have made them popular materials for analytical devices, such as microfluidic chips for LC. In the past decade, miniaturization has been realized by developing lab-on-a-chip solutions, where several analytical processes can be integrated within a few square centimeters. In such systems, due to the small channels and articulated geometries, the particle-packing procedure has proven to be challenging.(5) In contrast, monolithic beds are usually created in situ by free-radical polymerization of monomers in the presence of porogens and they are well-suited for chip-based separations. The proliferation of microfluidic devices has spurred new interest in polymer monoliths for applications such as enzymatic reactors(6,7) and microfluidic mixers.(8) This development has been boosted by the advent of additive manufacturing (or 3D-printing), which allows for rapid prototyping of complex structures, converting computer-aided-design (CAD) models into physical objects. Unfortunately, the use of 3D-printed analytical devices for chromatographic analysis is limited by the solvent compatibility of some materials (e.g., acrylate-based polymers) and in some cases by their transparency at the desired wavelength (e.g., UV or IR wavelengths). Several successful steps have been taken to locally photopolymerize monolithic stationary phases in discrete regions of microfluidic devices.(9−12) Heat is an alternative way to transfer energy to the monomer precursors for initiating the polymerization. However, accurate control of temperature in small confined spaces is more difficult to achieve, and so far only few steps have been taken in this direction.(13) In this work, two methods are explored to achieve confined thermal polymerization. The first approach involves direct contact (DC) between Peltier elements and the surface of a titanium device. In the second approach, recirculating jackets are used for localized heating and cooling (heating/cooling jackets, HCJ). The latter approach resembles a recirculation-based freeze–thaw valve.(14) In both approaches, defined hot (HR) and cold (CR) regions are created. We aim to fabricate poly(styrene-co-divinylbenzene) (PS-DVB) monolithic stationary phases within a 3D-printed titanium microfluidic device through polymerization at 70 °C, and to separate intact proteins using this device.